Through the proposed research, we will determine the mechanisms by which the parasympathetic fibers of the vagus nerve exert their rate-controlling influence on the heart. We will investigate the influence of the vagus nerve on the membrane potentials and ionic currents associated with the pacemaker activity of the sino-atrial (S-A) node. Development of new and novel methods will be required for voltage clamping S-A cells having functional vagal innervation. We will use the data from the voltage-clamp investigations to construct a mathematical model of cardiac pacemaker activity that will allow for vagal control of heart rate by suitable and biologically realistic modification of model parameters. This model will be valuable for future investigations of cardiac arrhythmias induced or aggravated by parasympathetic influences on the heart and by pharmacological agents and for investigations of the importance of cholinergic factors in the actions of drugs used for treating supraventricular arrhythmias.